The voltage-sensitive sodium channel alpha subunit, Scn8a, which is expressed in brain and spinal cord, was discovered in our laboratory as the gene responsible for motor endplate disease (med) in mice. Mice lacking Scn8a show ataxia and progressive hind limb paralysis, leading to death by 3-4 weeks. Although neurons contain several voltage-gated sodium channels, the loss of this single sodium channel alpha subunit results in a lethal phenotype, suggesting that Scn8a has unique properties which are essential for survival. These unique properties could be the result of a distinctive subcellular distribution and/or functional characteristics. The major goal of this proposal is to identify the unique functional domain(s) of Scn8a by construction of chimeric sodium channels and assay of their ability to correct the lethal phenotype of med mice in vivo.